2023-08-14 02:26:06
The identification of a subpopulation of tumor cells responsible for the recurrence of colorectal cancers in the form of metastases opens up new therapeutic avenues.
Surgical resection is the standard treatment for colorectal cancers and can cure most patients diagnosed with a localized tumour.
Despite everything, these cancers recur in a significant proportion of patients: approximately 5% of patients operated on for stage I colorectal cancer, 15% for stage II and 40% for stage III will in fact develop metastases in the following years. Reducing the incidence of these recurrences is therefore an absolute priority to improve the survival rate of patients with colorectal cancer.
Tumor subpopulation
Research in recent years has revealed that tumors are complex heterogeneous amalgams of multiple distinct populations of cancer cells, each of which uses different genes to drive cancer growth.
This obviously complicates the treatment of the disease, insofar as even if a therapeutic approach can succeed in completely eliminating one of these populations, another can resist it and thus allow the tumor to reappear following treatment.
To identify the subpopulation of tumor cells responsible for post-surgical recurrence of colorectal cancers, a team of researchers examined the genes preferentially expressed in tumor samples from patients who had suffered recurrences of their cancer.(1)
Individual cancer cell analysis (single cell transcriptomics) revealed that the majority of these genes were present in a specific population of tumor cells, named HRC (high-relapse cells), i.e. cells with a high rate of recurrence.
Metastatic recurrence
Subsequent experiments performed on model systems indicate that these HRC cells are the major contributors to post-surgical metastasis.
The researchers observed that HRC cells not removed by surgery gave rise to a variety of cancer cells with high metastatic potential.
Conversely, elimination of one of the main genes (EMP1) found in HRC cells completely abolished the appearance of metastases following surgical removal of the tumour.
Immune vulnerability
A very important aspect of the study is to show that despite their strong metastatic potential, HRC cells that migrate to peripheral organs are however deprived of an optimal tumor microenvironment to allow their growth.
This deficiency seems to make these cells very vulnerable to the action of the adaptive immune system (by cytotoxic T lymphocytes), since the addition of neoadjuvant immunotherapy (before surgery) considerably decreases the incidence of post-surgical metastases.
According to the authors, the use of the many forms of immunotherapy that have become available in recent years might achieve similar results in patients and have a dramatic impact on their likelihood of survival.
Cancer is a disease of rare complexity, which often requires a combination of several therapeutic approaches to succeed in defeating it. A challenge that research manages to meet more and more often, each of these small gains paving the way to the final victory once morest this disease.
(1) Cañellas-Socias A et coll. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells. Nature 2022 ; 611 : 603-613.
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